Threshold and Kinetic Differences between Fifth- and Sixth-Generation High-Sensitivity Cardiac Troponin T in Routine...

High-sensitivity cardiac troponin assays, such as troponin T (hs-cTnT), underpin the diagnosis and risk stratification of myocardial injury, with interpretation anchored to the 99th percentile upper reference limit (URL). As clinical laboratories transition from fifth-generation (Gen5) to sixth-generation (Gen6) hs-cTnT assays, analytical shifts may alter threshold crossing and timing of elevation near the 99th percentile URL, where clinical classification is highly consequential. However, real-world data describing the impact of this transition remain limited.

In this retrospective paired analysis, residual specimens from patients undergoing hs-cTnT testing were measured using Roche Gen5/Gen6 assays. A total of 3617 paired measurements from 1847 encounters (1737 patients) were analyzed longitudinally. Patient encounters were assessed for time to elevation above the 99th percentile URL; peak concentration; modeled 0-, 1-, and 3-hour pathway classification; and kinetic behavior.

Overall concordance between Gen5 and Gen6 was high for classification of hs-cTnT measurements and encounter peak values relative to the 99th percentile URL. Differences concentrated near the 99th percentile URL, where Gen6 crossed this threshold earlier than Gen5 and the converse was infrequent (2.6% vs 0.1%; P = 0.0001). In the modeled 0/1/3-hour rule-out/rule-in pathway, agreement between assays remained, although some encounters differed in classification between rule-out, indeterminate, and abnormal categories. Gen6 also demonstrated larger relative changes during the rising phase and steeper post-peak declines, with apparent elimination more similar to CK-MB than Gen5.

Gen5 and Gen6 hs-cTnT assays demonstrate strong overall agreement, although small analytical differences near decision thresholds produce measurable differences in timing of elevation and modeled clinical classification.